Optochemical sensor unit and a method for the qualitative and/or quantitative determination of an analyte in a measuring medium with the sensor unit

ABSTRACT

An optochemical sensor unit including: an optical waveguide; a transmitting unit for emitting a first transmission signal for exciting a luminophore; a receiving unit for receiving a received signal comprising a signal component emitted by the excited luminophore; a measuring chamber for receiving a fluid, wherein the fluid includes magnetic microspheres; a membrane arranged between the measuring chamber and a measuring medium for exchanging an analyte between the measuring medium and the fluid in the measuring chamber, wherein the measuring diaphragm is impermeable to the magnetic microspheres; and an electromagnet for attracting magnetic microspheres to a sensor membrane with a fluid-contacting surface and/or to a fluid-contacting surface of the optical waveguide, or to a surface of a transparent substrate layer of the optical sensor unit that is connected to the optical waveguide.

CROSS-REFERENCE TO RELATED APPLICATION

The present application is related to and claims the priority benefit ofGerman Patent Application No. 10 2018 126 082.2, filed on Oct. 19, 2018,and of U.S. patent application Ser. No. 16/654,288, filed Oct. 16, 2019,the entire contents of which are incorporated herein by reference.

TECHNICAL FIELD

The present disclosure relates to an optochemical sensor unit and amethod for the qualitative and/or quantitative determination, with theaforementioned sensor unit, of an analyte in a measuring medium.

BACKGROUND

The use of magnetic microspheres in a measuring medium is known per se.It is thereby problematic that a comparatively strong magnetic field isrequired to draw microspheres out of a measuring medium.

SUMMARY

Based on this preliminary consideration, it is the object of the presentdisclosure to provide a sensor unit for the use of magneticmicrospheres, which sensor unit may be operated with low energyexpenditure.

The present disclosure achieves the present object via the subjectmatter of claim 1 and via a method having the features of claim 15.Advantageous embodiments of the present disclosure are the subjectmatter of the dependent claims.

An optochemical sensor unit according to the present disclosurecomprises an optical waveguide, a transmitting unit for emitting a firsttransmission signal for exciting a luminophore, and a receiving unit forreceiving a received signal comprising a signal component emitted by theexcited luminophore.

The optochemical sensor unit is used for qualitative and/or quantitativedetermination of an analyte in a measuring medium. The analyte may bepreviously converted into a sensor-active substance. This can preferablybe accomplished catalytically or enzymatically. The sensor-activesubstance can then attach as quencher to the luminophore and reduce theluminescence, especially the fluorescence.

The optical waveguide can typically be designed as a fiber bundle. Theoptical waveguide is provided especially for signal transmission of thetransmission signal and the received signal. The transmitted signal isespecially a light signal which can be emitted by a signal source,especially a light source, for example an LED.

The receiving unit may be a photodiode. The principle of fluorescencequenching can preferably be used as the measuring principle of thesensor; however, the excitation of fluorescence is merely a variant ofthe measuring principle. The received light signal comprises a portionof excited radiation, for example fluorescent radiation.

The sensor unit has a measuring chamber for receiving a fluid, whereinthe fluid comprises magnetic microspheres. The fluid can, for example,be a solvent, for example water, with the microspheres. The measuringchamber is preferably a closed space with respect to a measuring medium.

The measuring chamber has a membrane which is arranged between themeasuring chamber and the measuring medium and which is provided forexchanging an analyte between the measuring medium and the fluid in themeasuring chamber. The membrane is thus analyte-permeable.

The membrane is impermeable to the magnetic microspheres. It ismicrosphere-impermeable.

The present disclosure differentiates between the aforementionedmembrane and a sensor membrane. The sensor membrane, insofar as it ispresent at all, is not a medium-contacting membrane and thus is not incontact with the measuring medium, but rather is a fluid-contactingmembrane. It is thus in contact with the fluid in the measuring chamber.Because the sensor unit can also be sold or stored with an unfilledmeasuring chamber, within the scope of the present disclosure the sensorunit is, however, protected independently of whether or not the fluid isarranged in the measuring chamber.

Instead of the sensor membrane, however, a transparent or translucentwall without further layers, or directly an optical waveguide, can alsobe provided. In this instance, the aforementioned wall can be designedanalogous to an uncoated substrate layer of a sensor membrane, forexample as a glass or quartz glass window.

The wall or the substrate layer as part of a sensor membrane canpreferably be formed as a transparent or translucent and conductivelayer of silicon oxide, indium tin oxide, graphene fibers, titaniumoxide, tungsten oxide, zinc oxide, tin oxide, vanadium oxide, and/orgallium oxide, or have such a layer.

The sensor unit has an electromagnet which is provided to attractmagnetic microspheres to the aforementioned sensor membrane or wall withfluid-contacting surface, and/or to an optical waveguide withfluid-contacting surface.

The measuring chamber provides a defined space in which the microspherescan come into contact with the analyte. The microspheres can then beattracted by a magnetic field of low strength. Moreover, during themeasurement a higher intensity can be achieved via the accumulation ofthe microspheres along the surface.

Advantageous embodiments of the present disclosure are the subjectmatter of the dependent claims.

It is advantageous if the optochemical sensor unit comprises a controlunit for controlling the electromagnet, wherein the control unit isdesigned to control the electromagnet between an activated anddeactivated state such that microspheres are attracted in the activatedstate and are not attracted in the deactivated state.

A deactivated state is thereby to be understood to mean that theelectromagnet also produces a repulsion of the microspheres, for examplevia polarity reversal. However, it is thereby difficult to achieveoptimal homogeneity of the microspheres in the fluid within themeasuring chamber. It is therefore especially advantageous if there isintermittently no magnetic field in the measuring chamber.

In the measuring operation of the sensor unit, however, it isadvantageous if the microspheres are attracted by the electromagnet.

The electromagnet can advantageously be arranged around an opticalwaveguide or in the optical waveguide, especially in a fiber bundle ofthe optical waveguide. In the first variant, the electromagnet can be inthe form of a coil which is arranged, especially wound, around theoptical waveguide. Alternatively, the electromagnet may also be formedas one or more magnetic fibers. The magnetic fiber may be a magnetizablefiber. If a plurality of magnetic fibers is present, they may includemagnetizable fibers. These fibers can be arranged between thelight-conducting fibers of a fiber bundle of an optical waveguide.

The electromagnet can alternatively or additionally be arranged in or ona sensor membrane. The electromagnet can preferably be arranged as aflat coil which can be designed as a single layer, for example as a coilprinted onto a substrate of the sensor membrane.

The sensor membrane may be designed as a substrate layer, preferably asa layer of silicon oxide, titanium oxide, tungsten oxide, zinc oxide,tin oxide, vanadium oxide, and/or gallium oxide. The substrate ispreferably transparent to the transmitting and/or receiving signal.

The sensor membrane can comprise further layers, for example ananalyte-sensitive layer which is arranged on the fluid side of thesubstrate layer. This analyte-sensitive layer comprises a luminophore.

Further optional layers are a reflection layer, diffusion barrier layer,and/or an optically insulating layer, a fluid-contacting cover layer,and, where appropriate, one or more adhesion promoter layers.

The electromagnet can be designed as a flat coil, preferably with arectangular or spiral configuration. The flat coil can be part,especially a layer, of the aforementioned sensor membrane.

The measuring chamber can preferably have an inlet and an outlet forexchanging the fluid in the measuring chamber so that microspheres, inwhich an embedded or attached enzyme or an embedded or attachedluminophore are consumed, can be exchanged.

The sensor unit can have an agitation device to homogenize the magneticmicrospheres in the fluid within the measuring chamber. Parts of theagitation device, for example a permanent magnet, which can be operatedby an agitator can advantageously be arranged in the measuring chamber.If undesired interactions with the magnetic microspheres occur, purelymechanical agitators can also be used as agitation devices.

The sensor unit can also have a metering and/or injection device for themetered addition of fluid into the measuring chamber, and/or foradjusting the concentration of microspheres in the fluid within themeasuring chamber. It is thus also possible to meter a plurality ofdifferent microspheres, for example separately with enzymes andanalyte-sensitive agents. For example, only one solvent for the fluidcan be supplied via the supply line, and the microparticles can bemetered in via the metering device.

As a magnetic substance, the microspheres may comprise a ferromagneticmaterial, preferably a material selected from a group comprising:elemental iron, cobalt, and/or nickel; nickel salts, cobalt salts,and/or iron salts; rare earth magnets, especially neodymium iron boron,samarium cobalt, samarium iron nitrogen alloys; strontium ferrites;and/or ferritic materials.

The magnetic substance may be arranged as a core of the microsphere,whereas a luminophore or a catalyst or an enzyme may be provided in acoating of the core.

The microspheres preferably have at least one agent for converting theanalyte into a sensor-active substance, preferably an enzyme and/or acatalyst, especially platinum.

The microspheres may comprise an analyte-sensitive material fordetecting the analyte, or may comprise an analyte-sensitive material fordetecting a sensor-active substance obtained by conversion of theanalyte. This can preferably be a luminophore-containing material,especially preferably a material comprising a fluorescent agent.

The microsphere may additionally comprise a capsule layer made of anatural material or of a synthetic polymer.

Furthermore according to the present disclosure is a method forqualitatively and/or quantitatively determining an analyte in ameasuring medium using a sensor unit according to the presentdisclosure, comprising the following steps:

introduction, into the measuring chamber, of a fluid comprising magneticmicrospheres having at least one agent for converting the analyte into asensor-active substance, and/or having an analyte-sensitive material fordetecting the analyte or a substance converted from the analyte;

at least in certain regions, introduction of the sensor unit into ameasuring medium, at least with the medium-contacting surface of themembrane;

activation of the electromagnet so that the microspheres accumulate on asensor membrane with a fluid-contacting surface and/or at afluid-contacting surface of an optical waveguide;

determination of a measurement signal while the microspheres haveaccumulated on the fluid-contacting surface.

After a single or repeated sequence of the aforementioned steps, acalibration can take place by introducing the optochemical sensor unitinto a fitting, or by temporarily sealing the analyte-permeable andmicrosphere-impermeable membrane which terminates the measuring chamber.This calibration can preferably take place as an in situ calibration inthe pipeline.

Further embodiment variants of the present disclosure are explained inmore detail below.

The control unit can be part of a measuring transducer, controlelectronics, and/or a power supply. The aforementioned elements can bepart of the sensor unit or part of a measuring device with the sensorunit.

The sensor unit and the remaining components of the measuring device canbe coupled to one another via a galvanically isolated connection,especially an inductive plug-in connector coupling and/or a radioconnection.

The energy for supplying the sensor unit can preferably be transmittedunidirectionally from further parts of a superordinate unit to thesensor unit via the galvanically isolated connection. The superordinateunit and the sensor unit thus form a measuring arrangement according tothe present disclosure.

The microspheres may especially be obtained from a natural productand/or a biopolymer.

The microsphere may contain a filler derived from natural materials.This filler may contain a reaction-accelerating substance, that is tosay an agent for converting the analyte, for example enzymes.

The particle size of the microspheres may preferably be in a rangebetween 1 and 1000 μm, insofar as an agent for converting the analyte isembedded.

The particle size of the microspheres may preferably be in a rangebetween 1 and 100 μm, provided that a sensor-specific dye or aluminophore is embedded.

The microspheres may contain additives for encapsulation, such astocopherol or cholesterol, made of vegetable and animal components. Theadditives are preferably harmless according to the FDA and/or GRASS, andpreferably contain no volatile components.

The aforementioned sensor membrane may include a polymer matrix, aluminophore, and a substrate. Further layers may optionally be providedin the sensor membrane, for example a layer having an optical insulator,a reflection layer, a diffusion-determining layer, or a hygienic layer.

The enzymes can be separately encapsulated in microspheres and containmagnetic particles, and be freely movable within the measuring chamber.

One or more of the microspheres may be provided with a magneticsubstance in the core and enzyme and/or indicator dye at the surface.The terms luminophore and indicator dye are to be understood assynonymous within the scope of the present disclosure.

The electromagnet and the luminophore may respectively be embedded in apolymer. This is also referred to as an “embedding matrix.” Theembedding matrix may preferably be a polymer having reactive functionalgroups. Within the scope of the present disclosure, for oxygen sensors,silicones are a preferred class of polymer having such groups. Forsensors with enzyme-containing layers, water-permeable polymers arepreferred, preferably such as polyurethanes, acrylamides, acrylates,and/or methacrylates.

As an alternative to the sensor membrane, the sensor can have atransparent or translucent wall, for example. This wall has a surfacefacing toward the measuring chamber, which surface can come into contactwith the fluid comprising the microspheres.

However, a sensor membrane with the aforementioned transparent ortranslucent wall is preferably used which represents a substrate layerand which is provided with an analyte-sensitive layer and/or furtherlayers, wherein these layers then have a surface which can come intocontact with the fluid comprising the microspheres.

As stated, only the transparent and/or translucent wall may also bepresent, on which wall further layers may, however, optionally bearranged, especially the aforementioned analyte-sensitive layer.

Furthermore, sensor-specific microspheres comprising an encapsulationmaterial with magnetic material and an analyte-sensitive agent,especially luminophore, can be present in the fluid, wherein themagnetic encapsulation materials are held in the region of the opticalwaveguide and/or the sensor membrane by a magnetic attractive force atleast during a measurement interval.

Alternatively, for example in the event of an optical pH measurement, areference dye, for example a phosphorophore, can also be contained inthe sensor membrane in addition to the indicator dye, for example afluorophore.

The sensor-specific components thus do not or do not all need to becontained in the sensor membrane, but can preferably be contained in themicrospheres which are loaded with magnetic particles.

These sensor-specific components are especially at least one analyteindicator in the form of a luminophore and/or at least one activator,for example an enzyme, for converting the analyte into a substance whichcan be measured by the sensor or a sensor-active substance.

Furthermore, the microspheres can contain at least one protectivematerial for the sensor-specific indicator dye. However, the protectivematerial can also be provided for protecting the enzyme.

The protective material may be in the form of a protective layer whichis arranged around the capsule material of the microsphere. Thesurrounding protective material may be an elastomer or a thermoplasticelastomer. Thermoplastics can also be used both as filling or wrappingmaterial for the microspheres.

To provide the microspheres, a natural product, for example spores, canbe relieved of internal constituents via hydrolysis. The resultinghollow bodies are used as capsule material for the microspheres. Forexample, a magnetic material may be incorporated in the interior of theencapsulation material, and an enzyme or luminophore may be arrangedalong the outer surface. However, other variants for attachment are alsoconceivable.

The inflow and/or outflow of fluid in the measuring chamber can bemonitored by a flow measuring device.

By sealing the measuring chamber of the sensor unit, an in situcalibration in the process may be enabled via a bypass.

A measuring arrangement according to the present disclosure comprises anoptochemical sensor unit according to the present disclosure and asuperordinate unit connected to the optochemical sensor unit, especiallya measuring transducer or a control electronics unit and/or a powersupply, wherein the optochemical sensor unit and the superordinate unitare coupled to one another via a connection, especially a releasableconnection, preferably an inductively coupling plug connector couplingand/or a radio connection; and wherein power is transmittedunidirectionally from the superordinate unit to the optochemical sensorunit via the connection.

The connection can advantageously be a galvanically isolated connection.

The superordinate unit can advantageously comprise a data processingunit, wherein additional data, especially the measurand, are transmittedbidirectionally between the optochemical sensor unit and thesuperordinate data processing unit via the connection.

BRIEF DESCRIPTION OF THE DRAWINGS

Further advantages, features and details of the present disclosure willbecome apparent from the following description, in which an exemplaryembodiment of the present disclosure is explained in more detail withreference to the drawing. The person skilled in the art will expedientlyalso consider the features disclosed in combination in the drawing, thedescription and the claims individually and combine them into reasonablefurther combinations. In the drawings:

FIG. 1 shows a schematic representation of an optochemical sensoraccording to the present disclosure;

FIG. 2 a shows a schematic representation of a modification of theoptochemical sensor of FIG. 1 ;

FIG. 2 b shows a schematic representation of the optochemical sensor ofFIG. 1 ;

FIG. 3 a shows a schematic representation of a first variant of a sensormembrane;

FIG. 3 b shows a schematic representation of a second variant of asensor membrane;

FIG. 3 c shows a schematic representation of a third variant of a sensormembrane;

FIG. 3 d shows a schematic representation of a fourth variant of asensor membrane;

FIG. 4 a shows a schematic representation of a first variant of aninserted microsphere;

FIG. 4 b shows a schematic representation of a second variant of aninserted microsphere;

FIGS. 5 a-5 c show a schematic representation of the distribution ofmagnetic material within a microsphere;

FIGS. 6 a-6 c show a representation of various modified variants of asensor according to the present disclosure; and

FIG. 7 shows a schematic representation of a calibration of the sensorof FIG. 1 , shown in positions A, B, and C.

DETAILED DESCRIPTION

Hereinafter, an optical sensor 1 according to the present disclosurewill be described using examples with reference to a possibleembodiment. The features, technical effects, and advantages mentioned inthis context can of course also be transferred to other optical oroptochemical sensors.

FIG. 1 shows an optochemical sensor unit 1, which can also be referredto as an optical sensor or as an optical sensor unit.

The measuring principle of the optochemical sensor unit 1 is based onthe principle of fluorescence quenching, and is explained in more detailbelow with reference to the determination of a concentration ofdissolved oxygen in the measuring medium.

The concentration of oxygen molecules in the sensor membrane, i.e. alsothe partial pressure of oxygen, is in equilibrium with the oxygenconcentration or the oxygen partial pressure in the measuring medium. Inthe measurement process, a first light signal with at least onecorresponding first wavelength is initially emitted to excite theluminophore molecules via the light source.

If the light signal impinges on the luminophore molecules, they areexcited and emit luminescence radiation which can be detected by thesensor unit 1 in the form of a second light signal.

If oxygen molecules are present in the sensor membrane, they interactwith the luminophore molecules and influence the emission of the secondlight signal (e.g. different intensity, different phase angles, ordifferent decay time). Thus, for example, energy is transmitted to theoxygen molecules via the second light signal. The intensity of thesecond light signal thereby decreases. This effect is also referred toas “quenching”, and the oxygen molecules are thereby what are known as“quenchers.”

The intensity, phase angle, or decay time of the second light signal isdependent on the concentration of quencher molecules. Of course, notonly oxygen molecules but also other molecules can be determined in thismanner, depending on which luminophore is used.

A fluorescent agent can especially serve as luminophore, but aphosphorescent agent can also be used in an analogous manner, so thathere a phosphorescence quenching is effected by quenching.

The optochemical sensor unit shown in FIG. 1 has a sensor housing 2.This sensor housing 2 is connected via a signal line 3 to an evaluationunit 4, which is preferably embodied as a measuring transducer.

The evaluation unit 4 is connected to a control unit 5. However, theevaluation unit and control unit can also be realized as one unit. Theoptochemical sensor unit 1 can have a coupling point along the signalline 3 for coupling to an evaluation unit 4.

The optochemical sensor unit 1 has a transmitting unit 6. Thistransmitting unit 6 has a light source 7 for emitting an optical signal,which light source 7 can comprise an LED, for example. Furthermore, theoptical sensor has a receiving unit 8, which can comprise a photodiode,for example, for receiving the changed optical signal, for example thesecond optical signal emitted by the luminescence dye (indicator dye)and influenced by luminescence quenching, and for converting the opticalsignal into a current- and/or voltage-equivalent measured value. In FIG.1 , in a compact design the receiving unit 8 is combined with thetransmitting unit 6 to form a transmitting and receiving unit.

The optical sensor 1 has a sleeve-shaped housing section 9 which isconnected to the receiving and transmitting unit 6. An optical guide 10or optical waveguide is routed within the housing section 9. The opticalwaveguide 10 directs the optical signal from the light source 7 to asensor membrane 11, or from the sensor membrane 11 to the receiving unit8. Furthermore, an adjusting unit 12, preferably a regulating unit, foradjusting an electromagnet can be arranged within the housing section 9.

Both the adjusting unit 12 and the receiving and transmitting unit 6 canbe connected directly or indirectly to the evaluation unit 4, forexample via a sensor coupling 27.

The optical sensor 1 has a magnet, preferably an electromagnet 14,preferably on the end face. The electromagnet 14 is operated withcurrent via the adjusting unit 12, wherein the reference current isadjustable via the adjusting unit 12. The electromagnet 14 may beactivated in a first operating state and deactivated in a secondoperating state.

The sensor membrane 11 is arranged on the end face of the housingsection 9 and, at the same time, forms a wall section of a measuringchamber 15. The housing section 9 is a structural unit of the sensorhousing 2 which can be detached from the supply and discharge lines 16,17. The measuring chamber 15 is provided to receive a fluid 50,preferably a liquid comprising an analyte and magnetic and/ormagnetizable microspheres 30, which are also referred to below as beads.These magnetic microspheres 30 are in particular ferromagnetic.Magnetizable microspheres are also to be understood as magneticmicrospheres in the sense of the present disclosure.

The fluid may additionally comprise at least one indicator and/or atleast one catalyst. The catalyst and/or the indicator can respectivelybe freely suspended in the solution, or in some instances may also bealso embedded in the magnetic microspheres 30. Two embodiment variantsof the magnetic microspheres 30 are schematically illustrated in FIGS. 4a and 4 b . In FIG. 4 a , the microsphere 30 comprises a core 35 ofmagnetic material, e. g., iron oxide, encased by a capsule material 36.This capsule material 36 represents the microsphere and is coated with aplurality of functional layers 31-34. An outer layer is formed as anenzyme layer 31 comprising an enzyme for converting the analyte. Anintermediate layer is designed as reflector layer 34.

FIG. 4 b shows an alternative microsphere 30 with a core 35 of magneticmaterial, e. g., iron oxide, encapsulated with capsule material. Anouter layer is formed as a cover layer 33, for example, for protectingthe underlying layers from mechanical and/or chemical effects, forexample from hydrolysis. A layer adjacent thereto is formed as an enzymelayer 31 comprising an enzyme for converting the analyte. Arrangedadjacent thereto is an indicator layer 32 comprising at least oneluminophore. A reflector layer 34 is then arranged between the reflectorlayer 34 and the capsule material of the microsphere 30 encasing thecore 35.

The indicator layer 32 of the microsphere 30 and the analyte-sensitivelayer 101 of the sensor membrane can preferably be constructed from thesame material.

Preferably only the magnetic constituents are encapsulated in thecapsule material 36, preferably natural substance capsules, for example,exines. The reflection layer or reflector layer 34 is preferablyarranged outside of the encapsulation material 36, wherein theencapsulation material is adjacent to the reflection layer. Theindicator layer 32 and in some instances an enzyme-containing layer orthe enzyme layer 31 are arranged on the reflection layer 34. Theenzyme-containing layer or enzyme layer may contain platinum particles.A layer with platinum particles for converting the analyte may also beprovided as an alternative to the enzyme layer. Of course, intermediatelayers and cover layers, for example the cover layer 33, areadditionally possible.

The magnetic substance in the microsphere 30 can be distributed indifferent ways. This is schematically illustrated in FIGS. 5 a-5 c .FIG. 5 a shows a concentration of the magnetic material in a core 35. Inaddition, the microsphere has the capsule material 36 of a microspherewhich encapsulates the magnetic core.

In the variant of FIG. 5 b , the magnetic particles 38 are arranged in adistributed manner within the capsule material 36.

In FIG. 5 c , magnetic particles 38 are arranged as a coating around apolymer core 37. The coated polymer core 37 is encapsulated with capsulematerial 36 to form a microsphere.

The encapsulation material 36 may be coated with further layers, such aslayers 31-34.

The measuring chamber 15 is arranged in a medium-tight manner relativeto the housing section 9 and can be filled and/or emptied via a supplyline 16 and a discharge line 17. At least one valve can respectively bearranged along the supply line 16 and the discharge line 17. In theexemplary embodiment of FIG. 1 , a valve 18 is respectively provided onthe supply and discharge lines 16 and 17, and in addition a respectivetap 13, e.g., a selector valve, is provided along each of the two linesfor optimum circulation.

A solvent 25 in particular can be supplied via the supply line. In someinstances, the solvent 25 may also already contain the indicator and/orthe catalyst. A metering unit 19 is arranged along the supply line 16,by means of which metering unit 19 the microspheres and, if not alreadypresent in the solvent, optionally also the catalyst and the indicatorcan be metered in. A thorough mixing within the measuring chamber 15 ispreferred. For this purpose, the sensor can have a mixing device which,in the present instance, can be a permanent magnet 26, colloquiallyreferred to as a magnetic stir bar, which can be operated by an agitatordevice, for example via the electromagnet 14. However, it is alsoconceivable to arrange the agitator device outside of the measuringchamber 15, wherein the microspheres themselves serve as magnets andenable a thorough mixing.

On the side opposite the sensor membrane 11, the measuring chamber 15 isdelimited by an analyte-permeable membrane 20. In the intended use, thismembrane 20 is arranged in a medium-contacting manner relative to theactual measuring medium 21. Apart from the analyte, it is preferablyimpermeable to the components located in the measuring chamber,including the microspheres, the indicator, and the catalyst.

The sensor membrane 11 itself is likewise magnetizable. The sensormembrane 11 can have a flat coil 22 for this purpose. The flat coil canhave a variety of shapes; for example, it can be designed as a spiral orrectangular coil.

The design of a sensor membrane 11 is handled in greater detail in FIGS.3 a-3 d , wherein FIGS. 3 a and 3 b show preliminary stages of a sensormembrane, and only FIG. 3 d shows a finished sensor membrane.

The sensor membrane is preferably of multilayer construction with aplurality of superimposed layers. These define a stacking direction. Thesensor membrane can be mounted fixed or be arranged in the measuringchamber 15 so as to be replaceable.

The sensor membrane 11 can have a transparent or translucent wall as asubstrate layer or substrate 100. The substrate can, for example,consist of silicon oxide or alternatively of titanium oxide, tungstenoxide, zinc oxide, tin oxide, vanadium oxide, and/or gallium oxide.

An analyte-sensitive layer 101, comprising a luminophore, can bearranged on the substrate 100 in the stacking direction towards themedium.

On the analyte-sensitive layer 101, the sensor membrane may have a fluidcontacting layer 102 for contacting the fluid 50 in the measuringchamber 15. Depending on the field of application, this fluid-contactinglayer 102 may have a polarity; for example, the layer 102 may designedto be superhydrophobic, hydrophilic or omni-phobic.

Further layers (not depicted) may also be present. This applies, forexample, to at least one reflection layer, diffusion layer, and/or anoptically insulating layer which may be arranged between thefluid-contacting layer 102 and the analyte-sensitive layer 101.

An adhesion promoter layer can respectively be arranged between theaforementioned layers. In FIG. 3 c , for example, such a layer 103 isarranged between the substrate 100 and the analyte-sensitive layer 101.

A layer having a second magnet, e.g., an electromagnet 104, is arrangedin the sensor membrane between the analyte-sensitive layer 101 and thefluid-contacting layer 102. The electromagnet 104 can preferably bedesigned as a flat coil, e.g., as a planar coil, and thus be part of thesensor membrane 11.

In the measuring principle of the sensor 1 according to the presentdisclosure of FIG. 1 , the microspheres can be brought into contact withthe surface of the sensor membrane 11 by activation, e.g., induction, ofa magnetic field. In this instance, the magnetic microspheres areattracted by the electromagnet 104 so that a local concentration of themicrospheres along the sensor membrane 11 occurs. Only after themagnetic field is established is a reproducible, interference-freemeasurement possible, even given low power consumption.

All possible measurement methods that can be used in the opticalmeasurement method, such as the determination of the decay time, phaseangle displacement, intensity change, and absorption changes, aresuitable as measurands for evaluation.

Parameters to be determined by the sensor 1 are preferably parameterssuch as glucose, lactose, and/or alcohol, which for measurement requireenzymes for conversion into a substance detectable by the sensor, suchas oxygen. The substance detectable by the sensor is also referred to asa sensor-active substance. Enzymes typically experience an aging givenstressing at high temperatures in a water-containing environment overlonger periods of time, which leads to degradation (hydrolysis)especially of the protein structure.

By incorporating the enzymes that are used into the microspheres, ahigher hydrolysis stability of the enzymes is achieved. In a preliminarystep, the incorporation can take place even before the microspheres areinserted in the sensor.

It can therefore be advantageous if the sensitive enzymes can either bestored outside the main stress zone, or be supplied back to the process,or be regenerated and supplied back, which is made possible by thepresent sensor according to the present disclosure.

In the embodiment variant of the sensor 1 with a sensor membraneaccording to FIG. 3 c , a flat coil can be mounted in the sensormembrane 11 or, alternatively, may be surface-mounted on the surface ofthe sensor membrane or the transparent or translucent wall. Acorresponding flat coil can thus, for example, be applied as a spiralstructure or a rectangular structure. In this instance, it is to benoted in the embodiment that a sufficiently active measuring surface isavailable for signal conduction, since the structures applied are nottransparent.

Ideally, therefore, the structure can be applied in the edge region ofthe sensor membrane and optimally cover only small areas in the actualmeasuring region of the analyte-sensitive region of the sensor membrane11.

The coil material can be arranged directly on the substrate, introducedinto the sensor membrane, or applied onto the membrane surface. Ideally,the structural design of the coil does not influence the light responsesignal.

What are known as flat coils can be a planar spiral coil, a planarwandering coil, a three-dimensional wandering coil, and/or a helicalcoil.

The coil can be located directly in front of the optical waveguide ofthe sensor, or on the side of the substrate of the sensor membrane thatfaces away from the medium, or on the medium-facing side of thesubstrate of the sensor membrane, or in another intermediate layer ofthe sensor membrane, or on the medium-contacting surface of the sensormembrane, in the direction toward the measuring chamber 15.

The electromagnet 104, in FIG. 3 c in the form of the flat coil, canadditionally be contacted with the substrate insofar as that it isconductive, for example if indium tin oxide layer or conductor tracesare present on or in the substrate. These layers can be sputtered, forexample.

Alternatively or additionally, the electromagnet 104 can also beoperated by the induction current of a second coil, for example also thecoil 14.

As an alternative to the sensor 1 shown in FIG. 1 , instead of thesensor membrane 11, it is also possible to provide only an opticalwaveguide with a terminal medium-contacting surface, e.g., an endsurface, or an optical waveguide having a substrate 100 (variant FIG. 3a ) with medium-contacting surface, an optical waveguide having asubstrate 100 and an analyte-sensitive layer 101 (variant FIG. 3 b )with medium-contacting surface, or an optical waveguide having asubstrate 100, an analyte-sensitive layer 101, and the fluid-contactinglayer 102 (variant FIG. 3 c ) with a medium-contacting surface. However,the medium-contacting surface of the optical waveguide or theanalyte-sensitive layer comes in contact, not with the measuring medium21, but rather with the fluid 50 in the measuring chamber 15 duringoperation of the sensor.

In the aforementioned alternative variants, an electromagnetic device oran electromagnet, for example, in the form of a coil, can be arranged inor around the optical waveguide. A magnetizable fiber or a wire, e.g.,one or more ferromagnetic fibers, can thereby be used, which arearranged between fibers of the optical waveguide or are wound around anoptical waveguide.

A coil can be arranged along the optical waveguide 10, for example, abundle of light-conducting fibers, on an end of the optical waveguide 10facing toward the medium. As already discussed above, it is also notabsolutely necessary to use a sensor membrane 11; rather, the opticalwaveguide can likewise have a fluid-contacting surface along which anelectromagnet can be arranged.

Of course, both the electromagnet 104 within the sensor membrane 11 andthe additional electromagnet 14 can be provided to attract themicrospheres, or respectively also only one of the two aforementionedelectromagnets.

The measuring chamber 15 is designed such that an exchange of analyte ispossible via the shown analyte-permeable but microsphere-impermeablemembrane 20. An exchange system enables the exchange of agedmicrospheres.

Optimally, the measuring chamber 15 has an agitation device forhomogenizing the solution in the measuring chamber, preferably with theelectromagnet 104 deactivated. Here, the permanent magnet as part of amagnetic agitator represents merely one embodiment variant for realizingan agitation device. In addition, other agitation devices, for examplemechanical agitation devices, can also be used.

Centrifugal agitation units or levitators can also be used as mixingapparatuses. Measuring devices can monitor the speed of agitation, forexample by flow measuring devices.

With regard to the microspheres, a plurality of variants for the sensor1 are conceivable, wherein structural details can vary with the type ofmicrospheres.

In a first embodiment variant of the sensor 1, the sensor membrane 11having at least one substrate 100 and one analyte-sensitive layer 101can be in direct contact with the optical waveguide 10 so that ananalyte, for example oxygen, can be measured. In this instance, however,the analyte is only a product or starting material of a chemicalreaction which indirectly detects the analyte that is actually to bedetermined. For example, an enzyme may be provided which releases orconsumes oxygen in a chemical reaction. Glucose oxidase (GOx or GOD)oxidizes glucose to glucolactone and hereby reduces the oxygenproportion in the system. The measurement of glucose can take place asan oxygen reference measurement. The loss of oxygen is accompanied bythe glucose concentration. The enzyme is hereby not so stable chemicallythat only the enzyme is contained in the microspheres in this instance.In this first embodiment variant, only the enzyme in the magneticmicrospheres is arranged in the measuring chamber 15 integrated in thesensor 1.

FIG. 2 b shows a corresponding variant with an arrangement as a sectionthrough a layer of the sensor membrane 11. In this instance, theelectromagnet 14 is provided for generation of the magnetic field toattract the microspheres, and a metallic grid 105 serves to conduct themagnetic field along the layer of the sensor membrane 11. This can, forexample, be arranged in the medium-contacting layer 102 of the sensormembrane 11.

In a second embodiment variant, the sensor 1 has only the substrate 100as a sensor membrane 11. In this instance, the microspheres contain theindicator, for example, a luminophore, which in the first embodimentvariant is located in the analyte-sensitive layer 101, and which in thesecond embodiment variant detects the analyte already in the fluid inthe measuring chamber 15.

In a third embodiment variant, the sensor 1 has only the substrate 100as sensor membrane 11. In this instance, the microspheres contain theindicator and the enzyme, which can be encapsulated jointly orrespectively by themselves in microspheres, so that microspheres withthe encapsulated enzyme and microspheres with encapsulated indicator canbe used, and in this instance the analyte content can be determinedindirectly as described with reference to the first embodiment variant.“Indirectly” thereby means that the enzyme degrades the actual analyte,and the analyte is then detected only via the change in a degradationproduct, such as the change in the oxygen content. Two measuring cellsor two sensors are also conceivable for a reference measurement, e.g.,one for oxygen without the analyte and one for the analyte, for examplefor glucose, by determining the differential content of oxygen.

Common to all microparticles or microspheres used in the variantsdescribed here is that they have magnetic substances (internal to themicrosphere) and overlying thereon a) an enzyme, b) an indicator dye, c)an enzyme, and a dye. By applying an electrical voltage to theelectromagnet in the sensor, the microspheres can be attracted andoptically measured.

The reference measurement can be made by a reference sensor. Thereference sensor may also be a simple optical oxygen sensor or DO sensor(dissolved oxygen sensor). In the event of two separate microspheretypes, the ratio between microspheres with the indicator layer tomicrospheres with the enzyme layer can be selected such thatsubstantially more microspheres are present with the enzyme layer,wherein the number of these microspheres is at least 50% higher,preferably twice as high, as that of the indicator layer microspheres.Thus, three preferred variants for the microspheres are obtained:

-   -   a) sensor having a membrane, which sensor comprises the        indicator and microspheres with an enzyme layer in the fluid;    -   b) sensor having a transparent or translucent wall and        microspheres with an indicator layer in or on magnetic        microspheres in the fluid;    -   c) sensor having a transparent or translucent wall and        microspheres with an enzyme layer and indicator layer in the        fluid.

The aforementioned electromagnet 104 or the electromagnet 14 forattracting magnetic microspheres may be formed as a coil. This coil maybe made of a diamagnetic, paramagnetic, and/or superparamagneticmaterial, such as iron, cobalt, nickel.

The optical waveguide fiber bundles can also be mixed with magneticcomponents. Ferroelectric materials, such as insoluble nickel, cobalt,and/or iron salts, rare earth magnets such as neodymium iron boron,samarium cobalt, samarium iron nitrogen alloys, strontium ferrites, orother ferritic materials, can also be present in the optical waveguide,for example as thin hollow tubes or fibers.

FIG. 2 a shows an arrangement of a metallic grid 105 within an opticalwaveguide 10, so that the magnetic field extends across the crosssection of the optical waveguide 10. A magnetic coil that can bearranged outside the optical waveguide 10 is not shown in this instance.

The aforementioned materials can thus be arranged in or along theoptical waveguide. Ideally, the arrangement should be such that theoptical properties of the optical waveguide are not disadvantageouslyimpaired.

For this purpose, the substances can be colored black, for example, orthe optical fiber bundles are adhesively bonded with a black adhesive.Given the use of fiber bundles consisting of optical waveguides andmagnetic fiber material, although the optically active area of theoptical waveguide is reduced, the magnetic effect on the sensor beads inthe solution increases.

In the illustrated embodiment variant, the sensor membrane 11 can be anordinary membrane of an optical oxygen sensor that can have a layercomprising a luminescent dye, e.g., a fluorescent dye, and an opticalinsulator. The optical insulator can, for example, be provided in afurther layer.

The magnetic microspheres can be natural substance-based capsules which,for example, are cell walls of algae, for example diatoms, or the exinesof pollen, or which can be obtained from spores, for example fungalspores. Alternatively, they can also be capsules based on a syntheticpolymer such as polystyrene divinylbenzene and derivatives thereof.These capsules can then be loaded with iron oxide.

In the above-described second or third embodiment variant, instead ofthe sensor membrane 11, a substrate composed of a transparent materialsuch as quartz glass or borosilicate glass, sapphire, or a plastic canbe used.

As previously described, the microspheres may be natural-based orsynthetic polymer-based capsules.

In the event of the second embodiment variant, they contain both themagnetic components, for example, in the form of iron oxide, and alsothe luminophore, for example, a fluorescent agent, and optionally anoptical insulator if the microsphere itself does not act like such.

The microsphere can likewise optionally comprise an enzyme, for example,glucose oxidase, which can preferably be provided in the outer region ofthe cavity. One possibility for arranging the enzyme on the microsphereis a coating. If necessary, this enzyme layer can also be coated with awater-permeable polymer, such as at least one polyvinylcarbazole, acrosslinked or un-crosslinked polyacrylamide, a polymethacrylate, ahydromethylcellulose, a polyethylene glycol, and/or apolyvinylpyrrolidone, or derivatives of the aforementioned compounds.This outer polymer layer can serve to produce a membrane on the surfaceof the microsphere and can preferably be designed to be permeable toglucose.

The magnetic microspheres that are used can be of different design.

Various illustrations of microspheres are shown in FIGS. 4 and 5 . Forthe production of capsules for the microspheres, a method can be usedwhich includes swelling and precipitating into a solvent, andevaporation of the solvent, spray drying, liquid encapsulation, or coreshell encapsulations.

An example of the preparation of various microspheres is listed below.

In order to prepare microcapsules, for example exines, for encapsulatingmagnetic substances, labile fluorescent materials such as proteins,lipids, nucleic acids, and carbohydrates must be extracted from startingmaterials such as spores. For this, lycopodium clavatum spores (250 g)can be suspended in acetone and boiled under reflux for 4 hours. Thedispersion is centrifuged and the supernatant is decanted. The defattedspores are stirred in 4% potassium hydroxide solution under refluxovernight (basic hydrolysis), then filtered, washed neutral with hotwater, and then washed colorless with ethanol. The base hydrolyzedsporopollenins are then dried overnight in the desiccator on phosphoruspentoxide. 150 g of the product thus obtained are suspended inorthophosphate solution (85%, 600 ml) and stirred under reflux for oneweek (acidic hydrolysis). The defatted, base- and acid-hydrolyzedsporopollenins are filtered, washed neutral with water, and washed againwith hydrochloric acid (200 ml), acetone (200 ml), and ethanol, andheated under reflux for 1 hour, filtered again, and dried in adesiccator with phosphorus pentoxide. The resulting exine is thentreated with sodium hypochlorite in order to obtain bright microspheresfor optical applications. The pretreated exines (5 g) are stirred in a10% sodium hypochlorite solution (250 ml) at 60° C. for 2 hours and,after being cooled, are filtered off and washed neutral with deionizedwater (approx. 1 liter). The exines are then washed with acetone (3×200ml) and ethanol (3×200 ml) and dried in a desiccator.

The microspheres are then loaded with iron oxide and/or enzymes and/orindicator dye, for example a fluorophore, or a reference dye, forexample a phosphorophore.

Admixed to a water-ethanol solution (9:1, 50 ml) are 10 g of an iron(III) chloride and 20 g of iron (II) chloride tetrahydrate and 5 ml ofhydrochloric acid (3M), and then 0.4 g of exines are added. Thedispersion is stirred vigorously for approximately 30 min at 45° C.,filtered and washed with deionized water, and then 25 ml of a 1M ammoniasolution are added. After 2 hours, the solution is filtered off andwashed with deionized water. After drying in the desiccator, thecapsules loaded with magnetic particles are added by drops to a 10%aqueous solution of glucose oxidase and bovine serum albumin (ratio 1:2v/v) in a 1% aqueous glutaraldehyde solution, and exines are added tothis solution. The dispersion is stirred at room temperature forapproximately 1 hour and then filtered and freeze-dried.

Optionally, the microspheres can also be loaded with a luminophore, forexample an indicator dye or reference dye, preferably with a fluorophoreor a phosphorophore.

In the context of the present disclosure, different optical measurementmethods are considered for determining the analyte concentration, forexample the measurement of the phase angle shift, the decay time, and/orthe intensity change. A concentration can be determined with afluorophore via the intensity change. The other two methods canpreferably use a phosphorophore in low power sensors. For certainmeasurements of ionic substances, a fluorophore is typically used as anindicator and a phosphorophore is used as a reference dye, for examplefor determining the pH value or an ion concentration.

The encapsulation of a luminophore is explained in more detail belowwith reference to an example:

Ruthenium tris(4,7-diphenyl-1,10-phenanathroline) trichloride (10 mg) isincorporated into dichloromethane (2 ml) and exines (1 g) of the batchand stirred on a magnetic agitator for approximately 2-3 min. Thedispersion is then slowly added by drops into water and stirred for afurther 2-3 min. The exines are then filtered and dried. Theencapsulation efficiency can be determined by weight gain oranalytically by means of extraction and HPLC. The hollow bodies thusproduced are dried in the desiccator and then dispersed withethanol/THF/water (80:10:10) and iron oxide, and are encapsulated andcollected by spraying with a spray gun into a preheated beaker.

The aforementioned example is merely one possibility for encapsulation.Microspheres that are markedly more complex can also be realized. Forsuch a more complex microsphere, the sensor components can be introducedinto the microspheres via successive encapsulation. An optimally highintensity can be detected by the sensor by means of the differentlayers.

At the same time, the microspheres can be freely attracted by theelectromagnet, so that a rapid, reproducible measurement is possible.

During production, a magnetic microsphere can first be provided ontowhich the further layers can then gradually be applied.

The plurality of variants of the microspheres will be explained in moredetail below. Initially, unloaded capsules are provided. The followingsteps can then be performed:

-   -   A) Loading with magnetic components, for example according to        the example described above    -   B) Optionally: Deposition of a reflective layer, preferably        comprising TiO₂, ZrO₂, or BaSO₄    -   C) Optionally: Application of a separation layer as a layer for        preventing particle migration of particles on the        analyte-sensitive layer (D) into lower layers    -   D) Application of the fluorescent dye or the analyte-sensitive        layer with the fluorescent dye    -   E) Optionally: Application of a diffusion barrier and/or a        hygienic layer,        -   for example by spraying and/or dipping, for example into a            diluted silicone polymer solution

The formation of the aforementioned separation layer can take place asfollows, for example: Titanium tetraethanolate (also known as titaniumethoxide) can be used as precursor, since TiO₂ is substantiallyinsoluble. Emulsion polymerization can be used for the coating. Additionof water initiates crosslinking. The formed TiO₂ then forms an insolublesub-layer on the capsule material of the microcapsule. ZrO2 can beapplied in a similar manner. A precipitation reaction can be used toapply barium sulfate. Here, BaCl2 and H2SO4 can be reacted.

Silicone, Teflon AF, Hyflon, and/or polyurethane can be used as thediffusion barrier layer, especially for ionic analytes.

For the incorporation of enzymes, polar substances such aspolyacrylates, polyethylene glycols (PEG), and/or polyvinyl alcohols(PVA) can be used.

TV silicones and/or polyurethane (PUR), among others, can be used as ahygienic layer.

A further variant for the production of loaded microspheres is describedbelow. Initially, unloaded capsules are provided. The following stepscan then be performed:

-   -   A) Loading with magnetic components, for example in accordance        with the example described above    -   B) Application of a reflection layer, for example a layer        containing TiO2-, ZrO2-, and/or BaSO4, in which is contained a        luminophore, for example a fluorescent dye. Alternatively, an        analyte-sensitive layer may be applied.    -   C) Optionally: Application of a diffusion barrier or a hygienic        layer, for example by dipping into a diluted silicone solution        (hexane as solvent) or into a fluoroalkylsiloxane solution

Various variants of the embodiment of the membrane 20 will be explainedin more detail below.

For example, the membrane 20 is formed from a polymer membrane that ispermeable to the analyte. In this example, the membrane 20 is connectedto the remaining sensor housing. However, a plurality of alternativeembodiments are possible. For example, the membrane 20 can also beformed as a porous wall of the sensor housing, for example by a wallregion which has one or more through-holes, for example nanoholes, andwhich terminates the measuring chamber 15. Alternatively, the membrane20 can also be formed by a wall or layer of a porous and/orion-conducting substance that terminates the measuring chamber 15, forexample a molecular sieve, a zeolite material, a ceramic, an ionexchanger, a proton conductor, an MOF (metal organic framework), and/ora ZIF (zeolitic imidazolate framework). The membrane 20 may be formedintegrally with the sensor housing 2 or may be fixedly connected to thesensor housing.

FIGS. 6 a-6 c show different variants of a sensor 1. According to FIG. 6a , it can be constructed in one piece, as has also already beenillustrated in FIG. 1 .

However, the membrane 20 can also be a component of a membrane cap 40which can be connected to a housing body so as to be detachable, as wasindicated schematically in FIG. 6 b . In this embodiment, a housing body39 and the membrane cap 40 together form the sensor housing 2 and themeasuring chamber 15, and the membrane cap 40 terminates the sensorhousing 2 and the measuring chamber 15 formed therein in the directionof the measuring medium. The membrane cap 40 is thereby slipped onto therest of the sensor housing 2.

If the membrane 20 is formed from a porous material, for example, aporous ceramic or zeolite, as shown in FIG. 6 c , it can be formed inthe form of a cap 41 partially or entirely made of the porous material,which is connected, for example by a plug or screw connection, to theremaining housing body 39 so as to be detachable, so that the capterminates the measuring chamber 15 on the side of the measuring medium.

In this embodiment, a rapid analyte exchange is possible between themeasuring fluid and the indicator contained in the measuring chamber. Itis hereby advantageous if the auxiliary substances possibly contained inthe indicator solution cannot pass through the membrane 20 in thedirection of the measurement medium. The porous ceramic can beexternally provided with an analyte-selective polymer coating, and/orinternally with a deposit-repellent coating.

Optionally, the ceramic may contain polymers which act selectively withrespect to the analyte, such as specific acrylamides and/orhydroxycellulose. The separation generally takes place via sizeexclusion.

In general, the membrane 20 should be protected from interferingsubstances such as proteins or dye molecules. However, in a preferredembodiment the medium-contacting membrane 20 can therefore also alreadybe analyte-selective. However, this is not necessarily predeterminedwithin the meaning of the present disclosure.

In the simplest instance, almost everything that is also present in themeasuring medium is present in the measuring chamber, with the exceptionof large abrasive materials or materials which tend to block themembrane 20 and/or may cause a falsification of the measurement. Themembrane 20 is intended primarily to prevent the magneticmicrospheres/beads from escaping from the measuring chamber 15. The termanalyte-selective is to be understood as an additional function of acoarse particulate and/or substance filter.

Various variants of the embodiment of the measuring chamber 15 will beexplained in more detail below.

The optical sensor unit 1 may comprise at least one optical waveguidefor guiding radiation emitted by the transmitting unit or the radiationsource into the measuring chamber 15, and for guiding luminescenceradiation from the measuring chamber 15 to the receiving unit.

Via a first fluid line, the supply line 16, the measuring chamber 15 canbe fluidically connected to at least one reservoir arranged outside themeasuring chamber 15, which reservoir contains magnetic microspheresloaded with indicator and/or enzyme. The reservoir may be provided aspart of a metering unit 19. The measuring chamber 15 can be fluidicallyconnected to a second fluid line, the discharge line 17. The seconddischarge line 17 can be connected to a collecting container (not shownin detail) for collecting spent microspheres. In this embodiment, themicrospheres present in the measuring chamber 15 can be exchanged atregular time intervals, as needed, or continuously for microspheres fromthe reservoir of the metering device 19. For this, the sensor unit 1 maycomprise means for transporting fluid from the reservoir into themeasuring chamber and for transporting fluid from the measuring chamber15 into the discharge line 17. These means may comprise valves, pumps,sloping fluid conduits, or other means for generating pressure gradientsalong which fluid can be transported. The at least one reservoir of themetering unit 19 and/or the collection container can be arranged withinthe sensor housing 2. Alternatively, the reservoir and/or the collectioncontainer may be arranged outside of the sensor housing 2. In thisinstance, the supply line 16 and the discharge line 17 are routed out ofthe sensor housing 2 in order to fluidically connect the reservoir ofthe metering unit 19 and/or the collection container to the measuringchamber 15.

Advantageously, the reservoir arranged in the measuring chamber 15 canbe fluidically connected to one or more, for example two or three,reservoirs (not shown) arranged outside the measuring chamber 15. Eachof the reservoirs may comprise an indicator and/or an enzyme which arebound, preferably encapsulated, within magnetic microspheres. Therespective microspheres of the respective reservoirs can differ from oneanother with regard to the indicator and/or the enzyme. For example, afirst reservoir may contain a type of microsphere loaded with anindicator and/or enzyme suitable for determining the concentration of afirst analyte, whereas a second reservoir contains a type of microsphereloaded with a second indicator and/or enzyme suitable for determiningthe concentration of a second analyte different from the first analyte.It is then possible, during operation of the sensor unit 1, toselectively introduce the first or the second indicator and/or catalystinto the measurement chamber 15 in order to determine the concentrationof the first or the second analyte by choice or in alternation. In thisinstance, the membrane 20 is designed in such a way that both the firstand the second analyte pass through the membrane 20 into the measuringchamber 15. In addition, in this embodiment the measuring chamber 15 isconnected to at least one collecting container for collecting spentindicator and/or catalyst, into which collecting container the indicatorand/or catalyst can be discharged from the measuring chamber 15.

In addition, the spatially delimited measuring chamber can also be usedfor calibrating the microspheres, for example, as is shown in FIG. 7 ,if the analyte-permeable membrane 20 is configured so that it can bemechanically sealed, for example. For this purpose, starting frommeasuring position A, the sensor unit 1 can be moved from the measuringposition A, for example, in which the membrane 20 is located in acontainer, by return of the sensor unit 1 into a position C within afitting 200, or by movement of sensor unit 1 out of the fitting 200until the membrane rests against a flat wall of the opposite side of thecontainer (position B). The container can be, for example, a pipeline ora reaction vessel, for example a fermenter. In the positions B and Cshown in FIG. 7 , the membrane 20 is temporarily sealed with respect tothe measuring medium located in the container. During this temporarysealing of the membrane 20, a standard containing the analyte can beadded into the measuring chamber, calibrated and washed, and a newstandard added, again calibrated and washed. During washing, theelectromagnet 104 may fix the microspheres so that only the calibrationsolution is exchanged. In this way, it is possible to perform aplurality of calibrations. Optionally, a separate oxygen referencesensor can be provided which can also be arranged in the measuringchamber, and which detects the oxygen content of the solution as areference value.

Claimed is:
 1. An optochemical sensor unit comprising: an opticalwaveguide; a transmitting unit configured to emit a first transmissionsignal for exciting a luminophore; a receiving unit configured toreceive a received signal comprising a signal component emitted by theexcited luminophore; a measuring chamber configured for receiving afluid, the fluid including magnetic micro spheres; an analyte membranedisposed between the measuring chamber and a measuring medium andoperative to exchange an analyte between the measuring medium and thefluid in the measuring chamber, wherein the analyte membrane isimpermeable to the microspheres; and an electromagnet operative toattract the microspheres to a surface of the optical waveguide, whichsurface is in contact with the fluid in operation, or to a surface of atransparent or translucent wall connected to the optical waveguide,which surface is in contact with the fluid in operation.
 2. Theoptochemical sensor unit of claim 1, further comprising a control unitconfigured to control the electromagnet between an activated state and adeactivated state such that the microspheres of the fluid are attractedin the activated state and are not attracted in the deactivated state.3. The optochemical sensor unit of claim 1, wherein the electromagnet isarranged around the optical waveguide or in the optical waveguide. 4.The optochemical sensor unit of claim 1, wherein the electromagnet isarranged within a fiber bundle comprising the optical waveguide.
 5. Theoptochemical sensor unit of claim 4, wherein the electromagnet includesone or more magnetic fibers among light-conducting fibers of the fiberbundle.
 6. The optochemical sensor unit of claim 1, wherein theelectromagnet is configured as a flat coil having a rectangular orspiral configuration.
 7. The optochemical sensor unit of claim 1,wherein the transparent or translucent wall comprises one or more ofsilicon oxide, indium tin oxide, graphene fibers, titanium oxide,tungsten oxide, zinc oxide, tin oxide, vanadium oxide, and/or galliumoxide.
 8. The optochemical sensor unit of claim 1, wherein the measuringchamber includes an intake and a discharge operable for exchanging thefluid in the measuring chamber.
 9. The optochemical sensor unit of claim1, further comprising an agitation device operable for homogenizing themagnetic microspheres in the fluid within the measuring chamber.
 10. Theoptochemical sensor unit of claim 1, further comprising a meteringand/or injection device configured to meter an addition of fluid intothe measuring chamber and/or to adjust a concentration of themicrospheres in the fluid in the measuring chamber.
 11. The optochemicalsensor unit of claim 1, wherein the microspheres include a magneticsubstance in the form of a ferromagnetic material, the material selectedfrom a group consisting of elemental iron, cobalt and/or nickel, nickelsalts, cobalt salts and/or iron salts, rare earth magnets, neodymiumiron boron, samarium cobalt, samarium iron nitrogen alloys, strontiumferrites, and ferritic materials.
 12. The optochemical sensor unit ofclaim 1, wherein the microspheres include at least one enzyme and/orcatalyst operable for converting the analyte into a sensor-activesubstance.
 13. The optochemical sensor unit of claim 1, wherein themicrospheres include an analyte-sensitive material operative fordetecting the analyte or a substance converted from the analyte, whereinthe analyte-sensitive material is a luminophore-containing materialand/or a material comprising a fluorescent agent.
 14. A measuringarrangement comprising: an optochemical sensor unit according to claim1; and a superordinate unit connected to the optochemical sensor unit,wherein the optochemical sensor unit and the superordinate unit arecoupled to each other via a connection, and wherein energy istransmitted unidirectionally from the superordinate unit to theoptochemical sensor unit via the connection.
 15. The measuringarrangement of claim 14, wherein the superordinate unit is a measuringtransducer, control electronics and/or a power supply.
 16. The measuringarrangement of claim 14, wherein the connection is reversible and is aninductive plug-in connector coupling and/or a radio connection.
 17. Themeasuring arrangement of claim 14, wherein the connection is aseparable, galvanically isolated connection.
 18. The measuringarrangement of claim 14, wherein the superordinate unit comprises a dataprocessing unit, and wherein data including values of the measurand aretransmitted bidirectionally between the optochemical sensor unit and thedata processing unit via the connection.
 19. A method for qualitativeand/or quantitative determination of an analyte in a measuring medium,the method comprising: a. providing an optochemical sensor unitaccording to claim 14; b. introducing into the measuring chamber thefluid including the magnetic microspheres, wherein the microspheresinclude at least one means for converting the analyte into asensor-active substance or an analyte-sensitive material for detectingthe analyte or a substance converted from the analyte; c. introducingthe sensor unit into the measuring medium; d. activating theelectromagnet such that the microspheres accumulate at thefluid-contacting surface of the optical waveguide or on thefluid-contacting surface of a transparent or translucent wall connectedto the optical waveguide; and e. determining a measurement signal whilethe microspheres have accumulated on the corresponding fluid-contactingsurface.
 20. The method of claim 19, wherein, after a single or repeatedsequence of steps (b) through (e), a calibration is performed byintroducing the optochemical sensor unit into a fitting or bytemporarily sealing the analyte membrane.
 21. The method of claim 20wherein the calibration is performed as an in situ calibration in apipeline.